If a creature loses hexproof in response to a spell targeting it, does the spell resolve?

Hexproof only matters at the moment a spell or ability is being cast or activated and targets are chosen (CR 508.1, 601.2c). Once a spell is already on the stack with legal targets, the game does not continuously re-check whether those targets have hexproof — that check is done at cast time and again only at resolution to verify the target is still legal in other ways (CR 608.2b).

Hexproof is not a targeting restriction that persists on the stack; it is a static ability that prevents a player from choosing that object as a target. If the creature loses hexproof after the spell has already been cast and placed on the stack, the spell already had a legal target when cast, so nothing invalidates it (CR 702.11b).

At resolution, the game checks whether each target is still a legal target (CR 608.2b). Legality at resolution does not include hexproof — hexproof only blocks targeting in the first place. So even if hexproof is somehow restored before resolution, it still would not cause the spell to be countered, because the creature was a legal target when the spell was cast.

Concrete example: Your opponent controls a 2/2 with Hexproof. You cannot target it. However, suppose the creature temporarily loses hexproof (e.g., via your opponent's own effect). You cast Lightning Bolt targeting it. In response, the creature regains hexproof. Lightning Bolt still resolves and deals 3 damage, because the target was legal at the time of casting and remains a legal permanent on the battlefield at resolution.

Key rules: CR 601.2c (targeting rules on cast), CR 608.2b (legality check at resolution), CR 702.11b (definition of hexproof).